This pilot study adds to the understanding of interventions to manage acculturative stress experienced during undergraduate study abroad programs. It was designed to evaluate the impact of cognitive behavioral strategy training combined with intentional practice during mixed reality (MR) simulations on acculturative stress. Participants included a convenience sample of undergraduate nursing students enrolled in a faculty-led study abroad course. Students participated in two MR simulations within a virtual environment over back-to-back days. Simulations were written by nursing faculty experts to reproduce realistic clinical situations students may encounter while studying in Peru. The Generalized Self-Efficacy Scale, State-Trait Anxiety Inventory, and Slater-Usoh-Steed questionnaire were administered. Quantitative biometric indices assessed during simulations included estimates of heart rate, blood pressure, respiratory rate, oxygen saturation and alterations in sweat gland activity reflective of changes in emotional state (galvanic skin response). There were changes in biometric indices within each simulation, but indices were not different between pre- and post- cognitive behavioral strategy training. Intentional reflective writing before, during, and after the study abroad program demonstrated an iterative cycle of reflection on action and mindfulness. These qualitative data suggest that pre-departure cognitive based behavior stress management strategies paired with simulated practice prior to departure may be one way to help nursing students deal with acculturative stress during study abroad experiences.